Octreotide stimulates Ca++ secretion by the gallbladder: a risk factor for gallstones.

Abstract

Gallstone formation during octreotide therapy has been linked to elevated levels of gallbladder bile Ca++, a well-known prolithogenic factor. Although the subcutaneous administration of octreotide raises gallbladder bile Ca++ in prairie dogs, the mechanism for this effect is unknown. Octreotide has been shown to increase gallbladder Na+ and water absorption in Ussing chamber studies. Given the known effects of octreotide on gallbladder ion transport, we hypothesized that octreotide may also promote gallstone formation by stimulating gallbladder Ca++ secretion, thereby raising the lumenal concentration of biliary Ca++. After cholecystectomy, prairie dog gallbladders were mounted in Ussing chambers, and standard electrophysiologic parameters were recorded. Unidirectional fluxes of Ca++ and Na+ were measured before and after serosal exposure to 50 nmol/L octreotide. Under basal conditions normal prairie dog gallbladder absorbed mucosal Ca++. Serosal octreotide converted the gallbladder from a state of basal Ca++ absorption to one of net Ca++ secretion by stimulating serosa to mucosa Ca++ flux. As anticipated, octreotide increased net Na+ absorption by stimulating mucosa to serosa Na+ flux and decreased tissue conductance and short-circuit current significantly compared with baseline values. Fifty nanomoles per liter octreotide stimulated Ca++ secretion by gallbladder epithelium, a possible mechanism for increased biliary Ca++ in prairie dogs receiving subcutaneous injections. Ca++ secretion linked to octreotide therapy may induce gallstones by raising biliary levels of Ca++, a known prolithogenic factor.